DUPIREAL: Two-Year Turning Point with Dupilumab in CRSwNP

In DUPIREAL, all patients started dupilumab with the recommended dosing, as an add-on therapy with intranasal corticosteroids for the treatment of adults with severe CRSwNP for whom therapy with systemic corticosteroids and/or surgery do not provide adequate disease control.^2,4 The recommended dose of dupilumab for adult patients is an initial dose of 300 mg followed by 300 mg given every other week.⁴

Key takeaways^2,4

Study design²

Figure 1. DUPIREAL study design.^2,3 *For 648 of patient’s data up to 12 months of treatment were collected retrospectively, and data beyond 12 months prospectively. 278 patients were followed retrospectively for 24 months. **Dupilumab interdose interval was extended from Q2W to Q4W in n=173 patients based on clinical reasoning. Q2W, biweekly; Q4W, every 4 weeks; ENT, Ear, Nose, and Throat.

Inclusion

Dupilumab for severe, uncontrolled CRSwNP: NPS ≥ 5 and/or SNOT ≥ 50, inadequate control with INCS, ≥ 2 cycles of systemic corticosteroid over the last year and/or a previous ESS.

Endpoints

2-year changes in clinical outcomes, safety, description of “late responders”, evaluation of dose tapering (Q2W vs. Q4W), reached disease control and remission.

Baseline characteristics²

Figure 2. Selected baseline characteristics of the study population. OCS, oral corticosteroids; NSAIDs, nonsteroidal anti-inflammatory agents.

Dupilumab effectiveness²

Primary and selected secondary outcomes

Figure 3. Primary and selected secondary outcomes on effectiveness of dupilumab for 24 months. NPS, nasal polyp score; SNOT-22, Sino-nasal Outcome Test-22; SSIT-16, Sniffin’ Sticks Identification Test-16; VAS, visual analogue scale.

Late responders

Dupilumab treatment response was delayed for some outcomes and patients. The results below demonstrate that patients with a slower onset of improvement can experience clinically meaningful improvement of symptoms in the long term.

Patients stratified by interdose interval

Dupilumab interdose interval was extended from Q2W to Q4W in n=173 patients based on varying clinical reasoning: (n=22 patients (12.7%) to manage minor adverse events, n=100 (57.8%) after achieving remission based on a shared decision with the patients and n=51 (29.5%) due to persistent blood eosinophilia, despite good clinical control and no eosinophilia-related AEs). There were no significant differences in effectiveness of dupilumab between the two dosing groups.

Response rate and remission

Based on the modified EPOS/EUFOREA 2023 criteria,

• At 12 months, 91.8 % (n=850) of patients were classified as good-to-excellent responders, while 7.0 % (n=65) as poor-moderate responders.
• At 24 months, 91.2 % (n=844) of patients were classified as good-to-excellent responders, while 7.7 % (n=71) as poor-moderate responders.

During the 24 months, the proportion of patients achieving disease control or remission steadily increased. The rate of patients with disease control/sustained control and on the way to remission/in remission, were defined based on 5 different scenarios with slightly different criteria:

Safety²

In total, n=175/926 patients (18.9%) experienced AEs, with mild to moderate AEs representing most cases (n=152/926, 16.4%). n=23/926 patients (2.4%) had severe AEs that resulted in treatment discontinuation.